Lanthanum trichloride: An efficient catalyst for the silylation of hydroxyl groups by activating hexamethyldisilazane (HMDS)

Article abstract of DOI:10.1016/j.jorganchem.2007.05.002

A variety of hydroxy functional groups was protected as their corresponding trimethylsilyl ethers using HMDS in the presence of lanthanum trichloride. The catalyst LaCl₃ activates the HMDS and accelerates the reaction under mild reaction conditions at room temperature to afford the corresponding silylated products in excellent yields.

Full text of DOI:10.1016/j.jorganchem.2007.05.002

Journal of Organometallic Chemistry 692 (2007) 3614–3618
www.elsevier.com/locate/jorganchem
Lanthanum trichloride: An efficient catalyst for the silylation
of hydroxyl groups by activating hexamethyldisilazane (HMDS)
Akkirala Venkat Narsaiah *
Organic Chemistry Division-III, Indian Institute of Chemical Technology, Fine Chemicals Laboratory, Hyderabad 500 007, India
Received 25 March 2007; received in revised form 26 April 2007; accepted 1 May 2007
Available online 8 May 2007
Abstract
A variety of hydroxy functional groups was protected as their corresponding trimethylsilyl ethers using HMDS in the presence of
lanthanum trichloride. The catalyst LaCl activates the HMDS and accelerates the reaction under mild reaction conditions at room tem-
3
perature to afford the corresponding silylated products in excellent yields.
Ó 2007 Elsevier B.V. All rights reserved.
3
Keywords: LaCl ; Hexamethyldisilazane; Protection of hydroxy group; Silylation ethers
1
. Introduction
Trimethylsilylation of hydroxy functional groups is a
main drawback is its poor silylating power, which needs
forceful conditions and long reaction times [4]. Therefore,
in sequential developments, to circumvent these problems,
considerable attention has been focused on activation of
hexamethyldisilazane by using a variety of catalysts [5].
Subsequently, Lewis acids are found to catalyze this reac-
tion under mild reaction conditions [6]. Recently, lantha-
num chloride emerged as an efficient Lewis acid catalyst
for various organic transformations [7]. We are especially
interested in exploring the potential use of lanthanum chlo-
ride due to its mild and neutral nature.
frequently used protection method in several chemical
transformations involving the synthesis of natural and
unnatural molecules [1]. Generally, the formation of silyl
ethers was carried out by the treatment of alcohols with
silyl chlorides or silyl triflates under the influence of basic
conditions [2]. However, some of these methods frequently
suffered from drawbacks such as the lack of reactivity or
the difficulty in removal of amine salts derived from the
reaction of by-product acids and co-bases during the silyla-
tion reaction. In the course of decades, a wide variety of
methods using 1,1,1,3,3,3-hexamethyldisilazane (HMDS),
a silylating agent have been developed [3]. Because, the
hexamethyldisilazane is a stable, commercially available
and cheap reagent for trimethylsilylation of hydrogen-
labile substrates, giving ammonia as the only by-product.
On the other hand, silylation using this silazane type
reagent is nearly neutral and does not need special precau-
tions. Even though the handling of this reagent is easy, its
2. Results and discussion
Herein, we wish to report an efficient procedure for the
rapid trimethylsilylation of a wide variety of alcohols using
hexamethyldisilazane and a catalytic amount of lanthanum
chloride as shown in the Scheme 1. For instance, the treat-
ment of glucose diacetonide with hexamethyldisilazane in
the presence of lanthanum chloride (10 mol%) at room tem-
perature to afford the corresponding trimethylsilyl ether
(entry t) in 80% yield without affecting the acetonide groups.
The reaction was completed within 4.0 h of reaction
1
*
time. The obtained product was very clean by H NMR
and did not require further purification. In a similar
Fax: +91 40 27160512.
E-mail address: vnakkirala2001@yahoo.com
0
022-328X/$ - see front matter Ó 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2007.05.002

A.V. Narsaiah / Journal of Organometallic Chemistry 692 (2007) 3614–3618
3615
-
O
LaCl Cl
2
O
O
O
HMDS-LaCI3
O
O
(Me Si) NH
+
LaCl3
(Me Si) NH
O
3
2
3
2
O
+
A
CH2Cl2 - R.T.
80%
Me SiO
O
3
HO
O
ROH
1
2
NH3
ROTMS
Scheme 1.
-
LaCl Cl
2
fashion, a wide range of structurally diverse and function-
alized alcohols, such as primary, secondary, benzylic, phe-
nolic, allylic and tertiary alcohols were underwent smooth
reaction to give the corresponding silyl ether derivatives in
excellent yields. Phenolic and benzylic alcohols were
reacted little faster than aliphatic alcohols (entry a, e, f,
h, n, o). The acid sensitive Baylis–Hillman alcohol (entry
q) was converted to the corresponding TMS–ether deriva-
tive without forming any side products. This protocol has
been used successfully where the acid sensitive protecting
groups like THP–ether and Boc-esters were present (entry
j, k, r). In such cases also the reactions were very clean
and did not yield any other products like deprotection of
the existing groups.
Sterically hindered alcohols (entry g, h, p, t) also reacted
very smoothly while giving the products in very good
yields. In the case of N-Boc amino alcohol (entry k) the
reaction is comparatively faster (3.5 h) and gave the corre-
sponding product in very good yield. The substrates like
cinnamyl alcohol (entry d) and octanyl (entry s) alcohols
also underwent smooth conversion. In general, the reac-
tions were carried out at room temperature and the solvent
used was methylenedichloride. All the reactions were com-
pleted within 3–5 h of reaction time and the obtained yields
were in 79–95%.
LaCl -NH
3
3
Me SiNH
3
2
+
B
ROTMS
ROH
Scheme 2.
of benzyl alcohol (1 mmol) and diphenyl methanol
1 mmol) was treated with hexamethyldisilazane
0.7 mmol), in the presence of catalyst, for a period of
(
(
3
.0 h. The observation shows that benzyl alcohol 85%
and the diphenylmethanol 15% converted to their respec-
tive silylether derivatives. In the third experiment, the
equimolar mixture of menthol and tert-amyl alcohol
was treated with HMDS (0.7 mmol) and the catalyst
for a period of 5.0 h. Only menthol was protected as sil-
ylether but tert-amyl alcohol was unaffected. The above
selectivity study shows that the reactivity order of ben-
zylic > primary alcohol > tertiary alcohol.
In summary, we have demonstrated that lanthanum
chloride as mild and efficient catalyst for the activation of
hexamethyldisilazane to silylate hydroxy functional
groups. This method is applicable to a wide range of alco-
hols having multi-functionalities. The experimental condi-
tions are very simple and the isolation of products also
very easy. The highly catalytic nature of lanthanum chlo-
ride and its wide applicability should make this protocol
an attractive alternative over existing methods.
The above probable mechanism shows that the lantha-
num chloride initially makes a complex with hexamethyl-
disilazane. The complex A will polarize the Si–N bond to
produce the reactive silylating agent, which on reaction
with one mole of alcohol gives the corresponding silyl
ether derivative. In a similar manner, another silyl por-
tion of the hexamethyldisilazane again forms a complex
B with the catalyst. This complex B on reaction with
another mole of alcohol gives the corresponding silyl
ether derivative. The mechanism clearly shows that one
mole of HMDS molecule reacting with two moles of
alcohols. Finally, the Cl La–NH complex, which ends
3
. General procedure for the silylation reaction
To a mixture of menthol (312 mg, 2 mmol) and hex-
amethyldisilazane (225 mg, 1.4 mmol) in methylenedichlo-
ride (10 mL) was added the catalyst lanthanumtrichloride
(
0.2 mmol). The resulting reaction mixture was stirred at
room temperature for a specified period (Table 1). The
progress of the reaction was monitored by thin layer
chromatography (TLC). After complete conversion of
the starting material as confirmed by TLC, the reaction
mixture was diluted by adding methylenedichloride
3
3
up with the evolution of gaseous ammonia and the recy-
cling of LaCl (Scheme 2).
3
The selectivity and versatility of the reaction was fur-
ther confirmed by application of the general procedure
for various examples (Table 2) in which, a mixture of
phenyl propanol (1 mmol) and menthol (1 mmol) was
treated with hexamethyldisilazane (0.7 mmol) in presence
of the catalyst. After stirring the reaction mixture for a
period of 5 h, found that 88% of phenyl propanol and
(
20 mL). The organic layer was washed with water and
brine then dried over Na SO and concentrated under
2
4
reduced pressure to afford the crude product, which
1
was conformed by its spectral data of H NMR, IR
and mass spectroscopy.
1
Spectral data for selected compounds. Compound 2g: H
1
2% of menthol were converted to their respective silyl
NMR (200 MHz, CDCl ): d 0.50 (s, 9H), 0.65 (s, 3H), 0.93
ether derivatives. In the second experiment, a mixture
3

3616
A.V. Narsaiah / Journal of Organometallic Chemistry 692 (2007) 3614–3618
Table 1
LaCl catalyzed silylation of alcohols by activating hexamethyldisilazene
3
a
b
S.No.
a
Substrate Products (2a–2t)
Reaction time (h)
3.0
Yield (%)
91
OH
OSiMe3
b
OH
OSiMe3
4.0
88
c
5.0
4.5
83
80
OH
OSiMe3
d
OH
OSiMe3
e
f
OH
OSiMe3
3.5
3.0
5.0
93
94
84
OH
CH3
OSiMe3
CH3
g
OH
OSiMe3
h
OH
OSiMe3
O
3.0
88
O
O
O
O
BnO
O
BnO
i
j
OEt
OEt
5.0
4.0
90
91
HO
Me3SiO
O
O
OH
NH
OSiMe3
N
N
Boc
Boc
k
Boc
OH
Boc
NH
3.5
85
OSiMe3
l
OH
OSiMe3
4.5
4.0
90
85
m
OH
OSiMe3
n
o
p
3.5
3.0
5.0
93
95
81
OH
OSiMe3
OH
OSiMe3
OH
OSiMe3

A.V. Narsaiah / Journal of Organometallic Chemistry 692 (2007) 3614–3618
3617
Table 1 (continued)
a
b
S.No.
q
Substrate
OH
Products (2a–2t)
Reaction time (h)
Yield (%)
2.5
86
OSiMe3
CO Et
CO2Et
2
r
4.0
79
OTHP
OTHP
OH
OSiMe3
O
s
t
4.5
4.0
83
80
OH
OSiMe3
O
O
O
O
O
O
O
HO
O
Me3SiO
O
a
1
All the products were characterized by H NMR, IR and mass spectroscopy and compared with literature reports.
Yields were isolated and unoptimized.
b
Table 2
Comparative study of silylation of alcohols using HMDS–LaCl
3
Entry
1
Alcohols
Products
Conversion (%)
88
Time (h)
5
OH
OSiMe3
+
+
CH3
CH3
1
2
OH
H C CH3
OSiMe3
3
H C CH3
3
2
OH
85
3
OSiMe3
+
+
OH
OSiMe3
1
5
3
CH3
CH3
100
5
OH
OSiMe3
H C CH3
H
3
C
CH
3
3
+
+
H C
H C
3
H C
3
3
0
OH
OSiMe
3
H C
3
CH3
CH
3
(
s, 6H), 0.98–1.20 (m, 4H), 1.30–1.40 (m, 1H), 1.60 (t, 2H,
(200 MHz, CDCl3):
d
0.50 (s, 9H), 1.20 (t, 3H,
J = 6.5 Hz), 1.85 (d, 1H, J = 6.5 Hz), 2.10–2.25 (m, 1H),
J = 6.5 Hz), 1.50–1.70 (m, 2H), 2.10–2.22 (m, 2H), 3.50
(t, 2H, J = 6.5 Hz), 4.10 (q, 2H, J = 6.5 Hz), 5.70 (d, 1H,
J = 11.0 Hz), 6.78–6.98 (m, 1H). EIMS. m/z (%). 231
1
3
.30–3.50 (m, 1H). Compound 2h: H NMR (200 MHz,
CDCl ): d 0.50 (s, 9H), 1.30 (s, 6H), 3.38 (d, 1H,
3
+
J = 3.5 Hz), 4.05–4.18 (m, 1H), 4.22–4.35 (m, 1H), 4.40–
(m , 12), 216 (20), 201 (10), 198 (12), 183 (15), 171 (10),
4
.55 (m, 2H), 4.95 (d, 1H, J = 7.5 Hz), 5.98 (d, 1H,
135 (22), 93 (45), 91 (100), 83 (65), 65 (40), 51 (32), 43
1
1
J = 3.5 Hz), 7.20–7.40 (m, 10H). Compound 2i: H NMR
(50). Compound 2j: H NMR (200 MHz, CDCl ): d 0.50
3

3618
A.V. Narsaiah / Journal of Organometallic Chemistry 692 (2007) 3614–3618
(
2
s, 9H), 1.20–1.35 (m, 2H), 1.40 (s, 9H), 1.60–1.90 (m, 2H),
.58–2.80 (m, 2H), 3.40–3.55 (m, 1H), 3.78–3.90 (m, 2H).
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(
1
Compound 2k: H NMR (200 MHz, CDCl ): d 0.50 (s,
3
(
9
9
1
(
5
H), 0.90 (two singlets, 6H), 1.25–2.35 (m, 2H), 1.45 (s,
H), 1.50–1.70 (m, 1H), 3.45–3.70 (m, 3H), 4.50 (br s,
1
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3
(
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.50 (s, 1H), 5.90 (s, 1H), 6.20 (s, 1H), 7.20–7.30 (m, 5H).
[
(
1
Compound 2t: H NMR (200 MHz, CDCl ): d 0.50 (s,
9
3
J = 3.5 Hz), 5.75 (d, 1H, J = 3.5 Hz). EIMS. m/z (%).
3
3
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+
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(
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(
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